Cutaneous adverse drug reactions in patients with congenital heart disease: a systematic review with focus on perioperative outcomes

Background: Cutaneous adverse drug reactions (CADRs) are uncommon but clinically significant complications among patients with congenital heart disease (CHD), particularly those with pulmonary arterial hypertension (PAH) or perioperative hemodynamic instability. The complex pharmacologic regimens required in CHD—often involving prostaglandins, vasodilators, antibiotics, and antiepileptics—predispose patients to idiosyncratic and immune-mediated reactions. Despite increasing recognition of CADRs in cardiovascular medicine, systematic evidence focusing on CHD populations remains limited. Methods: A systematic search of MEDLINE (PubMed), Embase, Web of Science, and CENTRAL was conducted from database inception to October 31, 2024, covering all types of congenital heart disease, both cyanotic and acyanotic, isolated and syndromic forms. Eligible studies included randomized controlled trials, observational studies, and case reports that reported CADRs in patients with structural CHD, regardless of age or surgical status. Extracted outcomes included type of CADR, implicated drug, temporal association, histopathology, management, and clinical outcome. Study quality was assessed using the Joanna Briggs Institute (JBI) checklist for case reports and case series. Results: Thirteen studies encompassing 27 patients met the inclusion criteria. Most patients (61%) were neonates or infants with duct-dependent CHD receiving prostaglandin E1 (alprostadil) for lesions such as transposition of the great arteries, hypoplastic left heart syndrome, and Taussig–Bing anomaly. The predominant CADRs included migratory urticaria and erythematous eruptions linked to prostaglandin E1 (n=8, 30%) and radiographically detected brown fat necrosis following prolonged infusion (n=5, 19%). Severe hypersensitivity reactions—including drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens–Johnson syndrome (SJS)—occurred in patients receiving vancomycin, carbamazepine, or levetiracetam (n=3, 11%), typically postoperatively or in intensive care. Other reports included bosentan-induced indurated erythema in an adult with repaired tetralogy of Fallot and amoxicillin-associated exanthema in pediatric post-repair patients. All studies scored low on JBI quality assessment due to descriptive designs and limited follow-up. The most frequently implicated drug classes were prostaglandin analogs (63%), antiepileptics (15%), and antibiotics (15%), with reaction patterns ranging from transient vasomotor erythema to immune-mediated hypersensitivity Conclusions: CADRs, though infrequently reported, occur across the therapeutic continuum of CHD management—from neonatal prostaglandin therapy to adult antimicrobial and antiepileptic use. The predominance of prostaglandin-associated reactions underscores the importance of dermatologic and metabolic surveillance during infusion therapy, while severe whereas severe hypersensitivity reactions underscore the interface between cardiology and dermatology. Larger multicenter studies are warranted to clarify incidence, risk factors, and outcomes, guiding safer pharmacologic management in congenital cardiology.